Date of Submission
Master of Science in Cellular and Molecular Biology
Biology and Environmental Sciences
Carter Takacs, Ph.D.
Anna Kloc, Ph.D.
Ellen J. Hoffman, MD, Ph.D.
Autism, ADNP Genes, Helsmoortel-Van Der Aa syndrome, Molecular Mechanisms
Autism Spectrum Disorder, Embryonic Development, Embryology
Autism spectrum disorders, Embryology, Genes, Behavioral embryology, Embryology, Experimental
Autism Spectrum Disorders (ASD) are a group of debilitating neurodevelopmental disorders, estimated to affect 1 in 54 children. Despite the identification of many autism-risk genes, the underlying mechanisms for ASD remain unclear. One of the most common forms of ASD is associated with de novo mutations in the ADNP gene (Activity-Dependent Neuroprotector Homeobox; accounting for 0.17% of ASD individuals). Termed ADNP syndrome, this disorder is characterized by intellectual disability, facial dysmorphia, and is comorbid with multiple organ system deficits. We set out to use zebrafish as a model organism to gain mechanistic insights into ADNP function. Zebrafish have the advantage of being high throughput, and have been established as a model for studying behavioral phenotypes and performing drug screenings in larvae. Zebrafish have two paralogs of adnp; adnpa and adnpb. This work characterizes the spatial and temporal expression of adnpa/b during zebrafish embryonic development, and details the establishment of a CRISPR/cas9 knockout line for adnpa/b in zebrafish. This work also presents preliminary data on CRISPR/Cas13d knockdown of adnpa and improvements in the efficiency of cas13d RNA knockdown. Future work aims to study the morphological and behavioral consequences of adnpa/b loss of function, as well as the molecular mechanisms by which adnpa/b impact zebrafish embryonic development.
Theune, William, "Using Zebrafish as a Model System for Studying the Autism Risk Gene adnp in Early Embryonic Development" (2021). Master's Theses. 177.